セレコキシブ 化學特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結晶
用途
選択的なシクロオキシゲナーゼ -2（COX-2）阻害剤です。
用途
セレコキシブ（Celecoxib, 日本における製品名：セレコックス）は、非ステロイド性消炎?鎮(zhèn)痛薬（Non-steroidal anti-inflammatory Drugs：NSAIDs）であり、100mgと200mgの錠剤がある。セレコキシブは、COX-2を選択的に阻害することを目的にドラッグデザインされ、日本でCOX-2選択的阻害剤としてカテゴライズされている唯一の薬剤である。
本においてセレコキシブは、2007年に関節(jié)リウマチ、変形性関節(jié)癥、2009年に腰痛癥、肩関節(jié)周囲炎、頸肩腕癥候群、腱?腱鞘炎の適応を取得した。また、2011年には急性疼痛として、手術後、外傷後、抜歯後の消炎?鎮(zhèn)痛の適応が承認された。日本以外の國では、強直性脊椎炎や月経困難癥などの適応ももっている。セレコキシブは鎮(zhèn)痛効果を発揮しつつ、従來のNSAIDsで見られるような消化管への副作用を最小限に抑えることを目的としてドラッグデザインされたCOX-2選択的阻害薬である。
セレコキシブの日本國內(nèi)における関節(jié)リウマチ、変形性関節(jié)癥、腰痛癥の第III相試験結果、および肩関節(jié)周囲炎、頸肩腕癥候群、腱?腱鞘炎の國內(nèi)一般臨床試験において、消炎?鎮(zhèn)痛効果で改善効果が認められた
用途
シクロオキシゲナーゼ2
（COX-2）選択的阻害剤です?？寡装Y?鎮(zhèn)痛
作用を示します。
効能
鎮(zhèn)痛薬, 抗炎癥薬, シクロオキシゲナーゼ2阻害薬
商品名
セレコックス (アステラス製薬)
説明
Celecoxib is a nonsteroidal antiinflammatory drug (NSAID) first
launched as Celebrex in the US for the treatment of symptoms in patients with
rheumatoid arthritis (RA) and osteoarthritis (OA). Celecoxib belongs to a new
class of 1, 5-diarylpyrazoles and can be synthesized by heat-promoted
heterocyclization of a trifiuoro-l,3-dione with appropriate arylhydrazine.
Celecoxib is a highly selective inhibitor of COX-2, the inducible form of
cyclooxygenase expressed during inflammatory processes; it does not block the
constitutive form COX-1, thus suppressing the gastric and intestinal toxicity of
most non-selective NSAIDs. The potency ratio COX1/COX2 on purified human
enzymes was about 400. In several in vivo models of acute and chronic
inflammation, Celecoxib demonstrated potent antiinflammatory activity without
affecting gastric or urinary prostaglandin PGE2. In several clinical studies
performed with patients suffering from osteoarthritis or rheumatoid arthritis,
Celecoxib was shown to be well tolerated and to relieve pain and inflammation more efficiently compared with other standard NSAIDs; the gastrointestinal
safety profile was significantly better than that of other NSAIDs. Interestingly,
Celecoxib was approved for another indication in patients with familial adenomatous polyposis (FAP). A six-month clinical trial
demonstrated a 28% reduction in the number of colorectal polyps with
Celecoxib, compared to a 5% reduction with placebo.
化學的特性
White to Pale Yellow Solid
使用
A selective cyclooxygenase-2 (COX-2) inhibitor. Anti-inflammatory. Used in treatment of familial adenomatous polyposis
適応癥
Celecoxib is indicated for the treatment of osteoarthritis
and rheumatoid arthritis. Its use is contraindicated
in individuals with hypersensitivity to sulfonamides
or other NSAIDs. It should be used with
caution in persons with hepatic disease. Interactions occur
with other drugs that induce CYP2C9 (e.g. rifampin rifampin)
or compete for metabolism by this enzyme (e.g.
fluconazole, leflunomide). The most common adverse
reactions to celecoxib are mild to moderate GI effects
such as dyspepsia, diarrhea, and abdominal pain.
Serious GI and renal effects have occurred rarely.
一般的な説明
Celecoxib (Celebrex) was the first selective COX-2 inhibitordrug introduced into the market in 1998 for use in thetreatment of RA, OA, acute pain, and menstrual pain. Thereal benefit is that it has caused fewer GI complicationswhen compared with other conventional NSAIDs. It hasalso been approved for reducing the number of adenomatouscolorectal polyps in familial adenomatous polyposis (FAP).Celecoxib is well absorbed and undergoes rapid oxidativemetabolism via CYP2C9 to give its inactive metabolites. Thus, a potential drug interaction exists betweencelecoxib and warfarin because the active isomer ofwarfarin is primarily degraded by CYP2C9.
生物活性
Selective cyclooxygenase-2 (COX-2) inhibitor (IC 50 values are 15 and 0.04 μ M for COX-1 and COX-2 respectively). Anti-inflammatory with shorter plasma half-life in vivo than SC 58121 (5-(4-Fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole ). Displays chemopreventive activity in in vivo tumor models.
薬物動態(tài)學
Celecoxib is well absorbed from the GI tract, with peak plasma
concentrations generally being attained within 3 hours of administration. Peak plasma levels in geriatric patients may
be increased, but dosage adjustments in elderly patients generally are not required unless the patient weighs less
than 50 kg.
臨床応用
Celecoxib is currently indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis and to
reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care.
Celecoxib is synthesized by condensing 4-methyl-acetophenone and ethyltrifluoroacetate with sodium methoxide and
the resulting butanedione derivative cyclized with 4-hydrazinophenylsulfonamide. It was the first NSAID to be
marketed as a selective COX-2 inhibitor.
合成
Celecoxib is prepared by condensation of 4-methylacetophenone with ethyl
trifluoroacetate to give 4,4,4-trifluoro-1-(4-
methylphenyl)butane-1,3-dione, which is cyclized with 4-hydrazinophenylsulfonamide.
代謝
Celecoxib is excreted in the urine and feces primarily as inactive metabolites, with less than 3% of an
administered dose being excreted as unchanged drug. Metabolism occurs primarily in the liver by CYP2C9 and
involves hydroxylation of the 4-methyl group to the primary alcohol, which is subsequently oxidized
to its corresponding carboxylic acid, the major metabolite (73% of the administered dose). The carboxylic
acid is conjugated, to a slight extent, with glucuronic acid to form the corresponding glucuronide. None of the
isolated metabolites have been shown to exhibit pharmacological activity as inhibitors of either COX-1 or COX-2.
Celecoxib also inhibits CYP2D6; thus, the potential of celecoxib to alter the pharmacokinetic profiles of other drugs
inhibited by this isoenzyme exists. Celecoxib, however, does not appear to inhibit other CYP isoforms, such as
CYP2C19 or CYP3A4. Other drug interactions related to the metabolic profile of celecoxib have been noted,
particularly with other drugs that inhibit CYP2C.
セレコキシブ 上流と下流の製品情報
原材料
準備製品